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High Doses of Beta Carotene Pose Lingering Threats

Supplement, once thought to prevent lung cancer, actually increases risk

TUESDAY, Nov. 30, 2004 (HealthDayNews) -- Twenty years ago, high doses of beta carotene were thought to have cancer-preventing power, and two large clinical trials were launched to determine if it might reduce lung cancer among cigarette smokers.

But the disease-fighting properties of beta carotene, a carotenoid which the body converts into vitamin A, fell far short, the studies found. One trial was even halted before its scheduled end because of the adverse effects of high doses of beta carotene supplement: it appeared to raise the risk of lung cancer, as well as death from heart disease and other causes.

Now, it appears that some of the adverse effects of high beta carotene doses can persist for women in particular, according to a study in the Dec. 1 issue of the Journal of the National Cancer Institute.

For the new study, researchers followed up with the participants in one of the trials -- the Beta-Carotene and Retinol Efficacy Trial (CARET) for six years after it ended in 1996.

They found the increased risk of death from heart disease disappeared quickly after the participants -- all smokers or former smokers or persons with a history of asbestos exposure -- stopped taking the supplements. However, the incidence of lung cancer and deaths from all causes decreased but didn't disappear. And former smokers and women had higher risk of lung cancer than did others in the study.

"CARET stopped a year and a half early," said Mark D. Thornquist, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, and a co-author of the new study. "Those who got the beta carotene [supplementation] had a higher incidence of lung cancer and overall mortality."

During the CARET study, the participants who took the supplement had a 28 percent greater incidence of lung cancer and 17 percent more deaths from all causes compared with those who didn't take the beta carotene. In the study, the beta carotene dose given was 30 milligrams a day, combined with 25,000 international units of retinyl palmitate, also thought to be a cancer fighter.

Thornquist and his colleagues followed the CARET trial participants to find out if the adverse effects of beta carotene went away as soon as people stopped taking the supplement.

The participants were contacted annually to update information on lung cancer and other health data, he said.

During this follow-up phase, women who took beta carotene were 1.3 times likelier to develop lung cancer than women who were on a placebo. They were also 1.4 times likelier to die of heart disease and 1.3 times likelier to die from all other causes.

"For men, the results of the vitamin went away within a year or so," Thornquist said. "In women, the effect appeared to be persistent."

Exactly why isn't known, he said, adding, "Men and women may have different abilities to repair DNA damage."

Hormonal differences may mean men and women metabolize beta carotene differently, he said. "Beta carotene tends to be stored in body fat, and women tend to have more body fat," he noted.

The results of the new study aren't surprising, said Anna Duffield-Lillico, an assistant attending epidemiologist at Memorial Sloan-Kettering Cancer Center in New York City, who co-authored an editorial accompanying the study. The fact that the risk of lung cancer and death was still elevated after use of the supplement was stopped "provides confirmation of the adverse effects of beta carotene supplements on lung cancer incidence in smokers."

High levels of beta carotene and exposure to cigarette smoke have proven a dangerous combination in animal studies, she said, leading to the rapid development of precancerous lesions.

The best advice, Duffield-Lillico and Thornquist agreed, is to avoid high doses of beta carotene. The CARET study's 30 milligrams a day is "about 10 times what you would get from a typical daily vitamin supplement," Thornquist said.

"We have no evidence that [the amount of beta carotene in] a typical multivitamin would be harmful," Thornquist added.

Beta carotene is found naturally in carrots, spinach and other dark-green leafy vegetables, broccoli and winter squash.

More information

To learn more about beta carotene, visit the National Library of Medicine.

SOURCES: Mark D. Thornquist, Ph.D., biostatistician, Fred Hutchinson Cancer Research Center, Seattle; Anna Duffield-Lillico, Ph.D., assistant attending epidemiologist, Memorial Sloan-Kettering Cancer Center, New York City; Dec. 1, 2004, Journal of the National Cancer Institute
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